Efficacy and safety of the Spiration Valve System™ for the treatment of severe emphysema in patients with Alpha-1 antitrypsin deficiency (EMPROVE).

OBJECTIVES: Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition associated with emphysema. This study analyzed the efficacy and safety of Spiration Valve System TM (SVS) among AATD patients with severe emphysema. METHODS: This multicenter prospective study included 20 patients demonstrating AATD as assessed by quantitative levels of AAT and genotype containing two ZZ alleles. Most diseased lobe based on high resolution computed tomography was selected for treatment with endobronchial SVS. The change from baseline in forced expiratory volume in 1 s (FEV1) at 6 months (Primary outcome) and at 12 months, quality-of-life (QoL) measured by St. George's Respiratory Questionnaire (SGRQ) as health status, dyspnea scale measured by mMRC, Chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), 36-item Short Form Health Survey (SF-36) physical component summary (PCS) and safety were assessed. RESULTS: Lung function (FEV1) significantly improved at 6 months (P = 0.02); but did not reach statistical significance at 12 months (P = 0.22). Significant improvement was observed in dyspnea (at all time points), QoL measures (3, 6, and 12 months), CAT score and PCS of SF-36 (1, 3 and 6 months). Response rates based on minimal clinically important difference reached 50-80% for all variables. Overall, 4.4 valves/patient were used to isolate the target lobe, with a mean procedure time of 20.3 min. Serious adverse events included COPD exacerbations (5%), pneumonia (10%), pneumothorax (15%) and death (5%), occurring within first three months. CONCLUSION: SVS endobronchial valve treatment showed improvement in lung function, dyspnea, and QoL in AATD patients with severe emphysema.

Sustained Clinical Benefits of Spiration Valve System in Patients with Severe Emphysema: 24-Month Follow-Up of EMPROVE.

Rationale: Follow-up of patients with emphysema treated with endobronchial valves is limited to 3-12 months after treatment in prior reports. To date, no comparative data exist between treatment and control subjects with a longer follow-up. Objectives: To assess the durability of the Spiration Valve System (SVS) in patients with severe heterogeneous emphysema over a 24-month period. Methods: EMPROVE, a multicenter randomized controlled trial, presents a rigorous comparison between treatment and control groups for up to 24 months. Lung function, respiratory symptoms, and quality-of-life (QOL) measures were assessed. Results: A significant improvement in forced expiratory volume in 1 second was maintained at 24 months in the SVS treatment group versus the control group. Similarly, significant improvements were maintained in several QOL measures, including the St. George's Respiratory Questionnaire and the COPD Assessment Test. Patients in the SVS treatment group experienced significantly less dyspnea than those in the control group, as indicated by the modified Medical Research Council dyspnea scale score. Adverse events at 24 months did not significantly differ between the SVS treatment and control groups. Acute chronic obstructive pulmonary disease exacerbation rates in the SVS treatment and control groups were 13.7% (14 of 102) and 15.6% (7 of 45), respectively. Pneumothorax rates in the SVS treatment and control groups were 1.0% (1 of 102) and 0.0% (0 of 45), respectively. Conclusions: SVS treatment resulted in statistically significant and clinically meaningful durable improvements in lung function, respiratory symptoms, and QOL, as well as a statistically significant reduction in dyspnea, for at least 24 months while maintaining an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Modulation of Mast Cell Reactivity by Lipids: The Neglected Side of Allergic Diseases.

Mast cells (MCs) have long been mainly regarded as effector cells in IgE-associated allergic disorders with potential immunoregulatory roles. Located close to the allergen entry sites in the skin and mucosa, MCs can capture foreign substances such as allergens, toxins, or noxious substances and are exposed to the danger signals produced by epithelial cells. MC reactivity shaped by tissue-specific factors is crucial for allergic responses ranging from local skin reactions to anaphylactic shock. Development of Th2 response leading to allergen-specific IgE production is a prerequisite for MC sensitization and induction of FcεRI-mediated MC degranulation. Up to now, IgE production has been mainly associated with proteins, whereas lipids present in plant pollen grains, mite fecal particles, insect venoms, or food have been largely overlooked regarding their immunostimulatory and immunomodulatory properties. Recent studies, however, have now demonstrated that lipids affect the sensitization process by modulating innate immune responses of epithelial cells, dendritic cells, and NK-T cells and thus crucially contribute to the outcome of sensitization. Whether and how lipids affect also MC effector functions in allergic reactions has not yet been fully clarified. Here, we discuss how lipids can affect MC responses in the context of allergic inflammation. Direct effects of immunomodulatory lipids on MC degranulation, changes in local lipid composition induced by allergens themselves and changes in lipid transport affecting MC reactivity are possible mechanisms by which the function of MC might be modulated.